Ligustrazine inhibits lipopolysaccharide-induced proliferation by affecting P27, Bcl-2 expression in rat mesangial cells.

Ligustrazine has a renoprotective effect against nephritis. In the present study, we investigated the roles of ligustrazine on lipopolysaccharide-induced changes of proliferation, cell cycle in cultured rat mesangial cells. 3-(4,5-dimethyltiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay revealed that rat mesangial cells treated with lipopolysaccharide (10mg/l) underwent significant proliferation compared with control group. This effect was significantly inhibited by ligustrazine (400 to 2500 mg/l). Flow cytometric analysis revealed that cells treated with lipopolysaccharide showed significant reduction in the ratio of G0/G1 phase and significant elevation in the ratio of S+G2/M phase. The changes of cell cycle induced by lipopolysaccharide were reversed by ligustrazine. In addition, lipopolysaccharide suppressed P27 protein expression was significantly increased by ligustrazine (100, 500, 2500 mg/l). Moreover, rat mesangial cells treated with lipopolysaccharide showed scanty apoptosis with up-regulation of Bcl-2expression, while Bax protein expression was not changed. Ligustrazine (100, 500, 2500 mg/l) significantly reversed lipopolysaccharide-induced up-regulation of Bcl-2 protein and increased apoptotic cell death. In summary, ligustrazine displayed a significant inhibiting effect on lipopolysaccharide-induced proliferation through increasing P27 and decreasing Bcl-2 protein expression in rat mesangial cells.